Intermittent Asthma Research Articles

Epidemiology, triggers, and severity of childhood asthma in Ilesa, Nigeria: Implications for management and control.

Background:Knowledge about childhood asthma in a locality will assist clinicians to adequately manage the condition. This study set out to report the epidemiology, triggers of exacerbation, comorbid conditions, and severity of childhood asthma at a tertiary health facility in Nigeria and the implication of these, in management and symptoms control.Methods:Over a 15-month study period, children (aged <15 years) with physician-diagnosed asthma were consecutively recruited at the pediatric chest clinic of the hospital. Sociodemographic history, triggers, and comorbidities in the children were recorded. The severity and level of symptoms control were determined using Global Initiative for Asthma criteria. The children were examined and had lung function test. Appropriate descriptive and inferential statistics were used to analyze the data obtained.Results:A total of 110 children were recruited for the study with an overall male preponderance 1.6:1, however, more adolescent females than males were observed. The ages of the children ranged from 10 months to 14 years with mean (standard deviation) of 6.4 (3.9) years. The median (interquartile range) age at diagnosis was 2.5 (1.5–6.0) years. The comorbidities were allergic rhinoconjunctivitis (45.5%), atopic dermatitis (10.9%), and overweight/obesity (7.3%). The recognizable triggers of exacerbations were respiratory tract infections (RTIs) seen more in preschool than school age children (χ2 = 6.225; P = 0.031), exercise, dust, and fumes. Mild intermittent asthma (82.7%) was the most common forms, 13 (25.0%) of the children who had Spirometry had obstructive ventilatory pattern and 17.3% had suboptimal asthma control.Conclusion:The majority of children with asthma at the Wesley Guild Hospital, Ilesa were school age children, however, 10% were <2 years and most asthmatics (72.7%) were diagnosed before age five. RTI is a major trigger of exacerbation and more than one-half had other allergic conditions which should be looked for and managed to ensure successful asthma management.

Factors associated with childhood asthma control in a resource-poor center.

Introduction:Optimal asthma control is a major aim of childhood asthma management. This study aimed to determine factors associated with suboptimal asthma control at the pediatric chest clinic of a resource-poor center.Methods:Over a 12-month study period, children aged 2–14 years with physician-diagnosed asthma attending the pediatric chest clinic of the Wesley Guild Hospital (WGH), Ilesa, Nigeria were consecutively recruited. Asthma control was assessed using childhood asthma control questionnaire. Partly and uncontrolled asthma was recorded as a suboptimal control. Relevant history and examinations findings were compared between children with good and suboptimal asthma control. Binary logistic regression analysis was used to determine the predictors of suboptimal asthma control.Results:A total of 106 children participated in the study with male:female ratio of 1.5:1, and majority (83.0%) had mild intermittent asthma. Suboptimal asthma control was observed in 19 (17.9%) of the children. Household smoke exposure, low socioeconomic class, unknown triggers, concomitant allergic rhinoconjunctivitis, and poor parental asthma knowledge, were significantly associated with suboptimal control (P < 0.05). Low socioeconomic class (odds ratio [OR] =6.231; 95% confidence interval [CI] =1.022–8.496; P = 0.005) and poor parental asthma knowledge (OR = 7.607; 95% CI = 1.011–10.481; P = 0.007) independently predict suboptimal control.Conclusion:Approximately, one in five asthmatic children attending the WGH pediatric chest clinic who participated in the study had suboptimal asthma control during the study. More comprehensive parental/child asthma education and provision of affordable asthma care services may help improve asthma control among the children.

Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study

Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the previous symptom-based cutoff for starting ICS by establishing whether there was a differential response to budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control across subgroups identified by baseline asthma symptom frequency. We did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study, done in 32 countries, with clinic visits every 3 months. Patients (aged 4-66 years) with mild asthma diagnosed within the previous 2 years and no previous regular corticosteroids were randomised to receive once daily, inhaled budesonide 400 μg (those aged <11 years 200 μg) or placebo. Coprimary outcomes for this analysis were time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator. Interaction with baseline symptom frequency was investigated, with patients grouped by more than two symptom days per week and two or fewer symptom days per week (divided into no days to 1 day, and more than 1 day to 2 days). Analysis was done by intention to treat. Of 7138 patients (n=3577 budesonide; n=3561 placebo), baseline symptom frequency was 0-1 days per week for 2184 (31%) participants, more than 1 and less than or equal to 2 symptom days per week for 1914 (27%) participants, and more than 2 symptom days per week for 3040 (43%) participants. For budesonide versus placebo, time to first SARE was longer across symptom frequency subgroups (hazard ratios 0·54 [95% CI 0·34-0·86] for 0-1 symptom days per week, 0·60 [0·39-0·93] for >1 to ≤2 symptom days per week, 0·57 [0·41-0·79] >2 symptom days per week, pinteraction=0·94), and the decline in postbronchodilator lung function was less at 3 years' follow-up (pinteraction=0·32). For budesonide versus placebo, severe exacerbations requiring oral or systemic corticosteroids were reduced (rate ratio 0·48 [0·38-0·61] 0-1 symptom days per week, 0·56 [0·44-0·71] >1 to ≤2 symptom days per week, and 0·66 [0·55-0·80] >2 symptom days per week, pinteraction=0·11), prebronchodilator lung function was higher, and symptom-free days were more frequent (p<0·0001 for all three subgroups), with no interaction by symptom frequency (prebronchodilator pinteraction=0·43; symptom-free days pinteraction=0·53). Similar results were noted when participants were classified by any guidelines criterion as so-called persistent versus so-called intermittent asthma. In mild recent-onset asthma, once daily, low-dose budesonide decreases SARE risk, reduces lung function decline, and improves symptom control similarly across all symptom subgroups. The results do not support restriction of inhaled corticosteroids to patients with symptoms on more than 2 days per week and suggest that treatment recommendations for mild asthma should consider both risk reduction and symptoms. AstraZeneca.

Can I get compensation, doctor?

Patients with possible occupational illness may ask their doctors about compensation. Here we describe two scenarios, osteoarthritis of the knee and asthma, in which this issue may arise, giving guidance on how to advise the patient. ### The patients Mr White, aged 58 years, has difficulty climbing ladders at work from a painful right knee. Examination shows signs of osteoarthritis, later confirmed radiographically. He has worked for 35 years as a building labourer, and enquires about compensation. Mrs Brown, aged 45 years, presents with intermittent asthma symptoms over 2 months, gradually worsening. Some of her colleagues in the factory where she works have had similar symptoms, and she wonders if it is work-related and compensable. ### Two common conditions How do you handle the compensation issue? First, establish a diagnosis and assess its influence on the patient’s life and job. This leads to a decision on management. It is necessary to consider causation, since if the work were responsible return might be inadvisable.1 Mr White’s job involves much climbing while carrying loads as …

Combined use of fractional exhaled nitric oxide and bronchodilator response in predicting future loss of asthma control among children with atopic asthma.

Recognition of patients at risk of asthma exacerbation is important for future asthma care and improved outcome. The aim of the present study was to see whether measurements of bronchodilator response (BDR) and fractional exhaled nitric oxide (FeNO) in combination provide prognostic information superior to either measurement alone in children with atopic asthma. A total of 201 atopic children aged 8-16 years with intermittent or mild persistent asthma were included. Pulmonary function tests including BDR and FeNO were serially monitored 10 times or more over 2 years when subjects were not receiving controller medications. After completion of monitoring, 1-year observation for a loss of asthma control was performed. During the monitoring period, positive BDRs (≥12% in forced expiratory volume in 1 s (FEV1 ) from pre-bronchodilator value) and FeNO higher than 35 parts per billion (ppb) were observed at least once in 59% and 77% of participants. When analysed as continuous variables, both BDR (hazard ratio (HR): 1.21; 95% CI: 1.04-1.41; P = 0.014) and FeNO (HR: 1.27; 95% CI: 1.09-1.49; P = 0.003) were associated with increased risks for a control loss. Compared with patients showing either positive BDRs (HR: 3.19; 95% CI: 1.05-9.64) or FeNO higher than 35 ppb (HR: 4.70; 95% CI: 1.68-13.11), patients with both findings (HR: 7.08; 95% CI: 2.57-19.49) had greater risks for a control loss. These data support that combined use of BDR and FeNO measurements can modify predictive risk obtained from either measurement alone.

Asthma Severity and the Controller Prescription in Children at 12 Tertiary Hospitals.

PurposeGuidelines need to be tailored to where they are applied. We aimed to describe the distinctive asthma severity profile and the pattern of controller prescription in Korean children.MethodsTwelve pediatric allergists from tertiary medical centers reviewed medical records of all asthmatic children who visited their clinics between September 1 and November 30 of 2013. Controller prescriptions were re-classified into 4 categories, then the prevalence of each asthma severity category and the controller prescription patterns according to asthma severity assessed by a Western (Global Initiative for Asthma, GINA) and an Asia-Pacific (Japanese Pediatric GuideLine, JPGL) guideline were evaluated.ResultsA total of 840 cases were reviewed. Both GINA and JPGL revealed that 328 (39.0%) and 249 (29.6%) subjects had intermittent asthma whereas 24 (2.9%) and 21 (2.5%) subjects had severe persistent asthma, respectively. Although higher category controllers tended to be prescribed to those who had more severe asthma, there was much overlap in categories of prescribed controllers between groups with regard to asthma severities. Leukotriene receptor antagonists (LTRA) was the most frequently prescribed as a single controller (40%) or as an add-on medication (19%) in the group of asthmatic children <6 years.ConclusionsKorean children have distinctive patterns of asthma severity and management strategies with a lower prevalence of severe asthma and a preference toward LTRA rather than low dose inhaled corticosteroids (ICS) alone or add-on long-acting beta-agonist (LABA) in the group of <6 year-old asthmatics that has not been predicted in Western countries. Thus, strategies tailored to regional situations need to be developed and recommended.

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma.

ABSTRACTObjective:To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. Methods:This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. Results:The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Conclusions:Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma.

The asthma-anxiety connection

BackgroundThe literature reports a significant association between various mental disorders and asthma, in particular depression and/or anxiety, with some more robust data regarding anxiety disorders. However, the nature of this association remains largely unclear. Objectives(1) To test the hypothesis of a specific association of anxiety and depressive disorder (according to the DSM-IV) with asthma and (2) to test the bidirectional hypothesis of causality between asthma and psychiatric disorders. MethodsNinety-six adults were compared with 96 control subjects matched according to main socio-demographic variables (i.e., gender, age, marital status, cohabiting/non-cohabiting, and BMI). Subjects with asthma were divided according to GINA and ACT classifications. All subjects underwent Structured Clinical Interviews for DSM-IV Axis I (SCID-I) diagnosis. ResultsSignificant association between asthma and lifetime anxiety disorders emerged (OR 3.03; p = 0.003); no significant association with other psychiatric diagnosis emerged. Moreover, lifetime and current anxiety were associated with asthma severity levels (p < 0.01 and p = 0.001 based on age). Asthma preceded anxiety in 48% of cases; in 52% of cases, anxiety preceded asthma, without significant group differences. The risk of asthma, particularly of severe, uncontrolled forms (p < 0.01), resulted higher in lifetime anxiety disorder patients (p = 0.003 and p = 0.001 based on age at onset). Current anxiety increased the risk of asthma, and that of an uncontrolled form (p < 0.05). Asthma increased the risk of lifetime anxiety disorders (p = 0.002 and p = 0.018 using ages). Intermittent asthma increased the risk of lifetime and current anxiety disorders (p < 0.01). ConclusionsAnxiety disorders, in particular Lifetime Anxiety Disorders, represent the only psychiatric disorder significantly associated with asthma, with a possible bidirectional, anxiety-asthma relationship, each of which can be caused or result from the other.

ASCIA‐P51: SAFETY OF 300IR 5‐GRASS POLLEN SUBLINGUAL TABLET FOR THE TREATMENT OF GRASS POLLEN‐INDUCED ALLERGIC RHINOCONJUNCTIVITIS IN ADULTS AND PEDIATRIC SUBJECTS WITH INTERMITTENT ASTHMA

Allergic asthma is frequently associated with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here we present the safety experience across the development program for the 300IR 5-grass pollen sublingual tablet by asthma status. Subjects with medically confirmed grass pollen-induced ARC were included in one of seven double-blind studies. Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists (GINA treatment Step 1) could participate. Adverse events (AEs) pooled from the studies were analyzed descriptively. Asthma status was recorded at randomization. The analysis included 1,878 adults and 312 pediatric subjects. Of these, 328 (17%) adults (300IR = 179, Placebo = 149) and 66 (21%) pediatrics (300IR = 32, Placebo = 34) had intermittent asthma at baseline. Percentages of actively-treated subjects reporting drug-related AEs were similar in those with and without asthma (adults: 59% vs. 58%; pediatrics: 53% for both). In both subsets, the respective incidences of AEs leading to discontinuation (mostly application-site reactions) were 6.7% vs. 4.3% (adults) and 3.1% vs. 4.9% (pediatrics). Of the subjects with asthma, 60 adults (300IR: 31/179 [17%]; Placebo: 29/149 [19%]) and 29 pediatrics (300IR: 14/32 [44%]; Placebo: 15/34 [44%]) reported an AE of asthma or a related symptom during treatment. Two actively-treated participants (including one pediatric) and 9 who received placebo (including one pediatric) were administered oral corticosteroids as treatment for an AE suggestive of asthma. There were no serious drug-related AEs in any subject with asthma who received 300IR. Treatment with 5-grass pollen sublingual tablet had a similar safety and tolerability profile in adults and children whether they had or not intermittent asthma.

ASCIA‐P49: SAFETY OF 300IR SUBLINGUAL TABLET OF HOUSE DUST MITE ALLERGEN EXTRACTS IN ADOLESCENTS WITH HOUSE DUST MITE‐ASSOCIATED ALLERGIC RHINITIS

Safety of house dust mite (HDM) sublingual tablets for the treatment of HDM-associated allergic rhinitis (AR) has been assessed across the clinical program. Here we present pooled safety data in adolescents treated with the 300IR dose. Adolescents (12–17 years) with medically confirmed HDM-associated AR were randomized in two Phase II/III double-blind studies conducted in Europe and Japan to receive a 300IR HDM tablet or placebo once daily for one year. Adverse events (AEs) were monitored throughout the studies and analyzed descriptively. 345 adolescents (300IR=173, Placebo = 172) comprised the Safety Set including 150 (43%) subjects with intermittent asthma at enrollment. The most commonly reported AEs during active treatment in the adolescents were mild or moderate application-site reactions such as throat irritation (13.9%), oral pruritus (9.8%) or mouth edema (8.7%). They occurred during the first day of treatment in nearly 20% of subjects and within the first month in about 50% of them. None of the serious AEs reported in 11 subjects (300IR=5, Placebo = 6) were considered drug-related. 18 subjects [300IR=12 (6.9%) and Placebo = 6 (3.5%)] withdrew due to an AE, mainly as a result of application-site reactions (e.g., upper abdominal pain, tongue edema). There were no reports of anaphylaxis and no use of epinephrine. Percentages of adolescents reporting at least one AE during active treatment or those reporting adverse reactions (ADRs) were similar in subjects with or without asthma [with asthma: 77% (AEs) and 50% (ADRs); without asthma: 78% (AEs) and 56% (ADRs)]. In both asthmatic and non-asthmatic subjects, the most frequent adverse reactions were those reported at the application site and were of similar incidences. A favorable safety profile of 300IR HDM sublingual tablets was demonstrated in adolescents with HDM-induced allergic rhinitis associated or not with intermittent asthma.

Nutritional status and physical inactivity in moderated asthmatics: A pilot study.

Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity.Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants.FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening.

Preventing Exacerbations in Preschoolers With Recurrent Wheeze: A Meta-analysis.

Half of children experience wheezing by age 6 years, and optimal strategies for preventing severe exacerbations are not well defined. Synthesize the evidence of the effects of daily inhaled corticosteroids (ICS), intermittent ICS, and montelukast in preventing severe exacerbations among preschool children with recurrent wheeze. Medline (1946, 2/25/15), Embase (1947, 2/25/15), CENTRAL. Studies were included based on design (randomized controlled trials), population (children ≤6 years with asthma or recurrent wheeze), intervention and comparison (daily ICS vs placebo, intermittent ICS vs placebo, daily ICS vs intermittent ICS, ICS vs montelukast), and outcome (exacerbations necessitating systemic steroids). Completed by 2 independent reviewers. Twenty-two studies (N = 4550) were included. Fifteen studies (N = 3278) compared daily ICS with placebo and showed reduced exacerbations with daily medium-dose ICS (risk ratio [RR] 0.70; 95% confidence interval [CI], 0.61-0.79; NNT = 9). Subgroup analysis of children with persistent asthma showed reduced exacerbations with daily ICS compared with placebo (8 studies, N = 2505; RR 0.56; 95% CI, 0.46-0.70; NNT = 11) and daily ICS compared with montelukast (1 study, N = 202; RR 0.59; 95% CI, 0.38-0.92). Subgroup analysis of children with intermittent asthma or viral-triggered wheezing showed reduced exacerbations with preemptive high-dose intermittent ICS compared with placebo (5 studies, N = 422; RR 0.65; 95% CI, 0.51-0.81; NNT = 6). More studies are needed that directly compare these strategies. There is strong evidence to support daily ICS for preventing exacerbations in preschool children with recurrent wheeze, specifically in children with persistent asthma. For preschool children with intermittent asthma or viral-triggered wheezing, there is strong evidence to support intermittent ICS for preventing exacerbations.

Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.

Asthma control and need for future asthma controller therapy among inner-city Hispanic asthmatic children engaged in a pediatric asthma disease management program (the Breathmobile program, Mobile Asthma Care for Kids Network)

Objective: To determine whether significant numbers of asthmatic children with initially rated intermittent asthma later suffer poor asthma control and require the addition of controller medications. Methods: Inner-city Hispanic children were followed prospectively in an asthma-specific disease management system (Breathmobile) for a period of 2 years. Clinical asthma symptoms, morbidity treatment, and demographic data were collected at each visit. Treatment was based upon National Heart, Lung, and Blood Institute (NHLBI) Expert Panel Report 3 asthma guidelines. Primary outcome was percentage of patients with intermittent asthma who had not well or poorly controlled asthma during subsequent visits and required controller agents. Secondary outcomes were factors associated with the maintenance of asthma control. Results: About 30.9% of the patients with initial rating of intermittent asthma had not well controlled and poorly controlled asthma during subsequent visits and required the addition of controller agents. Factors associated with good asthma control were compliance, no previous emergency room visits and previous visit during spring season. Conclusion: Asthmatic children with intermittent asthma often lose asthma control and require controller therapy. This justifies asthma guideline recommendations to assess asthma control at follow-up visits and adjust therapy accordingly.

Co-morbidities and cognitive status in a cohort of teenagers with asthma.

There is limited data regarding co-morbidities and cognitive status of asthma during childhood and adolescence. The aim of the current study was to explore the presence of co-morbidities and cognitive status in a large cohort of teenagers with asthma. The medical records of 314,897 consecutive 17-year-old males, undergoing comprehensive medical and cognitive evaluation prior to recruitment for military service, were reviewed. The prevalence of co-morbidities and a cognitive assessment in subjects with asthma were compared to those without asthma. Both a univariate and multivariate logistic regression analysis were performed. Active asthma was documented in 21,728 (6.9%) subjects: 3.3% were diagnosed with mild intermittent asthma, and 3.6% with persistent asthma. A significant positive correlation between a higher cognitive score and prevalence of asthma was found (P < 0.001), with a 55% increased prevalence of asthma in the subjects with the highest cognitive score compared to those with the lowest score. The following co-morbidities were significantly more prevalent in asthmatics compared to non-asthmatics: chronic rhinitis (35% vs. 5%), atopic dermatitis (2% vs. 0.4%), urticaria (1% vs. 0.3%), anaphylaxis (0.4% vs. 0.1%), chronic sinusitis (0.4% vs. 0.1%), overweight with body mass index (BMI) above 25 kg/m(2) (20% vs. 17%) and underweight with BMI less than 17 kg/m(2) (3.2% vs. 2.8%), irritable bowel syndrome (IBS) (1% vs. 0.5%), and thyroid disorders(0.4% vs. 0.2%). Chronic rhinitis and sinusitis, atopic dermatitis, IBS, and thyroid disorders were all significantly more prevalent in persistent compared to intermittent asthma (P < 0.001). In adolescence, a higher cognitive status was associated with a higher rate of asthma. Chronic rhinitis was the most prevalent co-morbidity and was found in one third of adolescent asthmatics. Other allergic diseases, chronic sinusitis, over and underweight, IBS, and thyroid disorders were also more prevalent in asthmatics. Pediatr Pulmonol. 2016; 51:901-907. © 2016 Wiley Periodicals, Inc.

Lessons learned from clinical trials of asthma.

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio can be associated with future exacerbations, although the FEV1 may be in the normal range, even with children who have persistent severe asthma. Asthma control questionnaires did not differentiate between children with or children without a future exacerbation. Alternatively, in adults, the lower baseline FEV1 (2.3 L [74% predicted] versus 2.5 L [78% predicted]) identified patients more likely to have a future exacerbation compared with patients who were not having an exacerbation. After correcting for FEV1, the asthma control questionnaire data were associated with exacerbations. In adolescents (ages ≥ 12 years) and adults with persistent mild asthma, most (73%) did not have sputum eosinophilia, and some of these patients responded well to the anticholinergic, tiotropium, which would argue differently from administration of an inhaled corticosteroid as first-line controller therapy. In a three-track study of patients with persistent mild asthma, as-needed budesonide-formoterol and scheduled budesonide were associated with approximately one-half of the annual exacerbation rate of as-needed albuterol. In patients with persistent moderate-to-severe asthma, tiotropium added to controller therapy caused an increase in FEV1 without improving the asthma control questionnaire findings. There were two studies that explored whether either quadrupling or quintupling the inhaled corticosteroid at the first sign of loss of control of asthma would provide meaningful reductions of severe exacerbations of asthma, but the findings did not support this strategy. Both biologic therapies and environmental control (dust mite impermeable encasings) have resulted in reductions of exacerbations in patients with persistent moderate and severe asthma.

Airway lipoxin A4/formyl peptide receptor 2–lipoxin receptor levels in pediatric patients with severe asthma

Lipoxins are biologically active eicosanoids with anti-inflammatory properties. Lipoxin A4 (LXA4) signaling blocks asthmatic responses in human and experimental model systems. There is evidence that patients with respiratory diseases, including severe asthma (SA), display defective generation of lipoxin signals despite glucocorticoid therapy. We investigated airway levels of formyl peptide receptor 2-lipoxin receptor (FPR2/ALXR), LXA4, and its counterregulatory compound, leukotriene B4 (LTB4), in patients with childhood asthma. We addressed the potential interplay of the LXA4-FPR2/ALXR axis and glucocorticoids in the resolution of inflammation. We examined LXA4 and LTB4 concentrations in induced sputum supernatants from children with intermittent asthma (IA), children with SA, and healthy control (HC) children. In addition, we investigated FPR2/ALXR expression in induced sputum cells obtained from the study groups. Finally, we evaluated invitro the molecular interaction between LXA4 and glucocorticoid receptor-based mechanisms. We found that children with SA have decreased LXA4 concentrations in induced sputum supernatants in comparison with children with IA. In contrast to decreases in LXA4 concentrations, LTB4 concentrations were increased in children with asthma independent of severity. LXA4 concentrations negatively correlated with LTB4 concentrations and with exacerbation numbers in children with SA. FPR2/ALXR expression was reduced in induced sputum cells of children with SA compared with that seen in HC subjects and children with IA. Finally, we describe invitro the existence of crosstalk between LXA4 and glucocorticoid receptor at the cytosolic level mediated by G protein-coupled FPR2/ALXR in peripheral blood granulocytes isolated from HC subjects, children with IA, and children with SA. Our findings provide evidence for defective LXA4 generation and FPR2/ALXR expression that, associated with increased LTB4, might be involved in a reduction in the ability of inhaled corticosteroids to impair control of airway inflammation in children with SA.

Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.

Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF-kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). B2R and NF-kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co-localization in 5B5(+) and αSMA(+) mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)-4/IL-13 with/without BK, and after NF-kB inhibitor, by Western blotting. Bronchial mucosa B2R and nuclear NF-kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls (P < 0.05), while B2R and NF-kB (total and nuclear) increased after allergen compared with after diluent (P < 0.05). Allergen exposure increased B2R expression in 5B5(+) and αSMA(+) cells. Constitutive B2R protein expression was higher in HABFb than in HNBFb (P < 0.05) and increased in both cell types after IL-13 or IL-4/IL-13 and BK treatment. This increase was suppressed by a NF-kB inhibitor (P < 0.05). Bronchial B2R expression is constitutively elevated in allergic asthma and is further increased after allergen exposure together with NF-kB expression. NF-kB inhibitor blocked IL-4/IL-13-induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti-asthma drug.

Calidad de vida y factores asociados en asmáticos de un centro de Atención Primaria. Aplicación de la versión reducida del Asthma Quality of Life Questionnaire

IntroductionAsthma is a highly prevalent disease that can affect the quality of life (QoL). The objective of this study is to determine the QoL in patients with asthma and its relationship with different factors in a Primary Care centre. Material and methodsA descriptive, cross-sectional study was conducted in an urban health centre. The study included a total of 243 patients between 17 to 70 years who had a diagnosis of asthma in their medical records. The QoL was measured using the Spanish version of the Mini-Asthma Quality of Life Questionnaire, with age, sex, smoking, anxiety, depression, severity and control of asthma as associated variables. ResultsThe mean age was 44.5 years and 71.2% were women. More than half (54.3%) had intermittent asthma, and 45.7% persistent asthma. The overall score in the Mini-Asthma Quality of Life Questionnaire was 5.4 out of 7. The scores by dimensions were: symptoms 5.4; limitation of activities 5.8; emotional function 5.7, and environmental stimuli 4.7. The variables with a worse QoL score that remained statistically significant (P<.05) in the multivariate analysis were poor control of asthma (in all dimensions), history of depression (in all except environmental stimuli), educated to less than secondary level (symptoms and emotional function), and patients admitted to hospital in the past 3 years (symptoms) and who used long-term beta-adrenergics (emotional function). ConclusionsPatients with intermittent, mild and moderate asthma have a good QoL. Poor control of the asthma and a history of depression negatively affect the QoL.

Effects of Traditional Chinese Medicine herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 to 5 years old

ObjectiveTo evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 and 5 years. MethodsA randomized, single-blind, placebo controlled trial was conducted. Children with intermittent asthma were enrolled and their baseline conditions were measured using a questionnaire. A total of 60 participants, aged 2 to 5, were randomized into either the treatment group (n = 40) or the placebo group (n = 20). The treatment group was treated with granules of TCM herbs for tonifying Qi and kidney, and replenishing spleen, and the placebo group was given placebo granules for 3 months. The number of asthma attacks was counted and TCM syndrome scores were measured at 1, 2, 3, 6, 9, and 12 months. The airway resistance and levels of eosinophil cationic protein for the two groups were observed before and after 3 months. The results were statistically analyzed. ResultsCompared with the placebo group, the number of asthma attacks significantly decreased in the treatment group (P < 0.05). For the treatment group, the TCM syndrome scores decreased after 1 and 2 months; there was also a significant difference in scores between the two groups (P < 0.05). The difference remained after the medicine was stopped for 9 months (P < 0.05). After the 3-month treatment, compared with the placebo group, the airway resistance decreased in the treatment group (P < 0.05). No adverse events were reported in the treatment group. ConclusionThe TCM herbs for tonifying Qi and kidney, and replenishing spleen reduced the number of intermittent asthma attacks, decreased the TCM syndrome scores, and reduced the airway resistance in the children aged 2 to 5.